Scientists Get the Lowdown On Sun’s Super-hot Atmosphere (Planetary Science)

Orbiting instrument hints at how stored magnetic energy heats solar atmosphere.

A phenomenon first detected in the solar wind may help solve a long-standing mystery about the sun: why the solar atmosphere is millions of degrees hotter than the surface.

Images of the sun captured by the IRIS mission show new details of how low-lying loops of plasma are energized and may also reveal how the hot corona is created. (Credit: Rice University/NASA)

Images from the Earth-orbiting Interface Region Imaging Spectrograph, aka IRIS, and the Atmospheric Imaging Assembly, aka AIA, show evidence that low-lying magnetic loops are heated to millions of degrees Kelvin.

Researchers at Rice University, the University of Colorado Boulder and NASA’s Marshall Space Flight Center make the case that heavier ions, such as silicon, are preferentially heated in both the solar wind and in the transition region between the sun’s chromosphere and corona.

There, loops of magnetized plasma arc continuously, not unlike their cousins in the corona above. They’re much smaller and hard to analyze, but have long been thought to harbor the magnetically driven mechanism that releases bursts of energy in the form of nanoflares.

Rice solar physicist Stephen Bradshaw and his colleagues were among those who suspected as much, but none had sufficient evidence before IRIS.

The high-flying spectrometer was built specifically to observe the transition region. In the NASA-funded study, which appears in Nature Astronomy, the researchers describe “brightenings” in the reconnecting loops that contain strong spectral signatures of oxygen and, especially, heavier silicon ions.

The team of Bradshaw, his former student and lead author Shah Mohammad Bahauddin, now a research faculty member at the Laboratory for Atmospheric and Space Physics at Colorado, and NASA astrophysicist Amy Winebarger studied IRIS images able to resolve details of these transition region loops and detect pockets of super-hot plasma. The images allow them to analyze the movements and temperatures of ions within the loops via the light they emit, read as spectral lines that serve as chemical “fingerprints.”

“It’s in the emission lines where all the physics is imprinted,” said Bradshaw, an associate professor of physics and astronomy. “The idea was to learn how these tiny structures are heated and hope to say something about how the corona itself is heated. This might be a ubiquitous mechanism that operates throughout the solar atmosphere.”

The images revealed hot-spot spectra where the lines were broadened by thermal and Doppler effects, indicating not only the elements involved in nanoflares but also their temperatures and velocities.

At the hot spots, they found reconnecting jets containing silicon ions moved toward (blue-shifted) and away from (red-shifted) the observer (IRIS) at speeds up to 100 kilometers per second. No Doppler shift was detected for the lighter oxygen ions.

The researchers studied two components of the mechanism: how the energy gets out of the magnetic field, and then how it actually heats the plasma.

The transition region is only about 10,000 degrees Fahrenheit, but convection on the sun’s surface affects the loops, twisting and braiding the thin magnetic strands that comprise them, and adds energy to the magnetic fields that ultimately heat the plasma, Bradshaw said. “The IRIS observations showed that process taking place and we’re reasonably sure at least one answer to the first part is through magnetic reconnection, of which the jets are a key signature,” he said.

In that process, the magnetic fields of the plasma strands break and reconnect at braiding sites into lower energy states, releasing stored magnetic energy. Where this takes place, the plasma becomes superheated.

But how plasma is heated by the released magnetic energy has remained a puzzle until now. “We looked at the regions in these little loop structures where reconnection was taking place and measured the emission lines from the ions, chiefly silicon and oxygen,” he said. “We found the spectral lines of the silicon ions were much broader than the oxygen.”

That indicated preferential heating of the silicon ions. “We needed to explain it,” Bradshaw said. “We had a look and a think and it turns out there’s a kinetic process called ion cyclotron heating that favors heating heavy ions over lighter ones.”

He said ion cyclotron waves are generated at the reconnection sites. The waves carried by the heavier ions are more susceptible to an instability that causes the waves to “break” and generate turbulence, which scatters and energizes the ions. This broadens their spectral lines beyond what would be expected from the local temperature of the plasma alone. In the case of the lighter ions, there might be insufficient energy left over to heat them. “Otherwise, they don’t exceed the critical velocity needed to trigger the instability, which is faster for lighter ions,” he said.

“In the solar wind, heavier ions are significantly hotter than lighter ions,” Bradshaw said. “That’s been definitively measured. Our study shows for the first time that this is also a property of the transition region, and might therefore persist throughout the entire atmosphere due to the mechanism we have identified, including heating the solar corona, particularly since the solar wind is a manifestation of the corona expanding into interplanetary space.”

The next question, Bahauddin said, is whether such phenomena are happening at the same rate all over the sun. “Most probably the answer is no,” he said. “Then the question is, how much do they contribute to the coronal heating problem? Can they supply sufficient energy to the upper atmosphere so that it can maintain a multimillion-degree corona?

“What we’ve shown for the transition region was a solution to an important piece of the puzzle, but the big picture requires more pieces to fall in the right place,” Bahauddin said. “I believe IRIS will be able to tell us about the chromospheric pieces in the near future. That will help us build a unified and global theory of the sun’s atmosphere.”

Reference: Bahauddin, S.M., Bradshaw, S.J. & Winebarger, A.R. The origin of reconnection-mediated transient brightenings in the solar transition region. Nat Astron (2020). https://doi.org/10.1038/s41550-020-01263-2

Provided by Rice University

Molecular Mechanism of Plant Immune Receptors Discovered (Botany)

Research team from the University of Cologne and the Max Planck Institute for Plant Breeding Research (MPIPZ) explore the activation of plant immune receptors by pathogens /similar function of immune receptors in plants and animals.

In a recent study, Alexander von Humboldt Professor Jijie Chai at the University of Cologne and his team together with MPIPZ researchers have succeeded for the first time in reconstructing the sequence of molecular events that activate an inactive plant immune receptor and thus mediate the death of the host cell. The researchers’ discoveries are of great importance for understanding how these critical plant immune molecules protect their hosts from infections. The configuration adopted by the activated protein is similar to that of other plant and mammal receptors, including humans. This suggests that these receptors are based on a common structural principle to trigger intracellular immune signals and cell death in different areas of life.

Figure 1 The RPP1 resistosome: a top view of the cryo-EM structure Tetrameric assembly of the RPP1 resistosome shown from the surface. The four RPP1 monomers are labeled and shown in different colors: ATR1 is shown in green; BB-loops that mediate formation of the asymmetric RPP1 TIR dimers are labeled and shown in red. ©University of Cologne

The scientists describe their results in the article ‘Direct pathogen-induced assembly of an NLR immune receptor complex to form a holoenzyme’ in Science.

Although separated by millions of years of evolution, plants and animals have independently developed similar immune strategies to protect themselves against microbial infections. In both kingdoms of life, immune receptors called nucleotide-binding/leucine-rich repeat proteins (NLR proteins) form an important defence layer within cells against pathogen attack. NLRs are complex devices consisting of several modules. These modules recognize the molecules (effectors) of invading microbes. Effectors trigger the immune response of the plant – they activate receptors, resistance and cell death pathways to limit infection. Based on different structural and signalling characteristics, plant NLRs are divided into two main classes: those that contain coiled-coiled (CC) modules (CNL proteins) and those that contain toll/interleukin-1 receptor/resistance (TIR) modules (TNL proteins).

The scientists conducted their research on the model organism Arabidopsis thaliana, or thale cress. Jijie Chai, together with the MPIPZ research group leader Jane Parker and MPIPZ dirctor Paul Schulze-Lefert, determined the structural and biochemical features underlying the activation of a specific receptor: the so-called TNL type NLR Receptor of Peronospora parasitica 1 (RPP1). It protects the model plant against infection with the fungus Hyaloperonospora arabidopsidis (Hpa).

To understand how RPP1 protects plants on the molecular level from Hpa infection, the team generated RPP1 protein together with the known Hpa effector ATR1 . The RPP1 receptor activated in this way is an enzyme that breaks down nicotinamide adenine dinucleotide (NAD+), which is important for defence signalling.

By isolating RPP1-ATR1 complexes and subjecting them to cryo electron microscopy, the authors have answered two open questions of NLR biology: first, how direct binding of the effector to the NLR receptor induces the activation of a receptor. Secondly, they determined that the TNL receptor in this case organizes itself as a so-called tetramer, a molecule consisting of four tightly packed receptor molecules. Tetramers belong to the group of oligomeric molecules, which are all structurally made up of similar units. The observed tetramer creates a unique surface within a part of the receptor, which is necessary for the cleavage of NAD+ to trigger defence signals.

The effector ATR1 induces tetramerization at one end of RPP1 and simultaneously forces the above-mentioned four TIR modules at the opposite end of the molecule to form two asymmetric TIR pairs that degrade NAD+.

Strikingly, the results of the groups around Eva Nogales and Brian Staskawicz at the University of California, Berkeley, on another NLR of the TNL type, Roq1 from the tobacco relative Nicotiana benthamiana, also show that TNL activation involves direct effector recognition and adoption of a similar tetrameric structure. The effector recognized by Roq1 is produced by a bacterial pathogen and the activated Roq1 receptor complex provides resistance to bacterial infections. Therefore, the discoveries of Jijie Chai, his team and the MPIPZ researchers seem to be of great importance for understanding how these critical plant immune molecules protect their hosts from infections. More generally, the oligomeric configurations adopted by active RPP1 and Roq1 resemble the induced oligomeric scaffolds of other plant and mammalian NLR receptor proteins, including human innate immune receptors. This suggests that these receptors are based on a common structural principle to trigger intracellular immune signals and cell death in different kingdoms of life.

Reference: Shoucai Ma, Dmitry Lapin, Li Liu, Yue Sun, Wen Song, Xiaoxiao Zhang, Elke Logemann, Dongli Yu, Jia Wang, Jan Jirschitzka, Zhifu Han, Paul Schulze-Lefert, Jane E. Parker, Jijie Chai, “Direct pathogen-induced assembly of an NLR immune receptor complex to form a holoenzyme”, Science 04 Dec 2020: Vol. 370, Issue 6521, eabe3069 DOI: 10.1126/science.abe3069 link: https://science.sciencemag.org/content/370/6521/eabe3069

Provided by University of Cologne

How The Brain Distinguishes Fact From Possibility (Neuroscience)

Our brains respond to language expressing facts differently than they do to words conveying possibility, a team of neuroscientists has found. Its work offers new insights into the impact word choice has on how we make distinctions between what’s real vs. what’s merely possible.

A full-brain analysis revealed a significant effect for modal force, eliciting stronger activity for the factual condition over the modal conditions. ©Tulling et al., eNeuro 2020

“At a time of voluminous fake news and disinformation, it is more important than ever to separate the factual from the possible or merely speculative in how we communicate,” explains Liina Pylkkanen, a professor in NYU’s Department of Linguistics and Department of Psychology and the senior author of the paper, which appears in the journal eNeuro.

“Our study makes clear that information presented as fact evokes special responses in our brains, distinct from when we process the same content with clear markers of uncertainty, like ‘may’ or ‘might’,” adds Pylkkanen, also part of the NYU Abu Dhabi Institute.

“Language is a powerful device to effectively transmit information, and the way in which information is presented has direct consequences for how our brains process it,” adds Maxime Tulling, a doctoral candidate in NYU’s Department of Linguistics and the paper’s lead author. “Our brains seem to be particularly sensitive to information that is presented as fact, underlining the power of factual language.”

Researchers have long understood that the brain responds in a variety of ways to word choice. Less clear, however, are the distinctions it makes in processing language expressing fact compared to that expressing possibility. In the eNeuro study, the scientists’ primary goal was to uncover how the brain computes possibilities as conveyed by so-called “modal” words such as “may” or “might”—as in, “There is a monster under my bed” as opposed to, “There might be a monster under my bed.”

To explore this, the researchers used formal semantic theories in linguistics to design multiple experiments in which subjects heard a series of sentences and scenarios expressed as both fact and possibility—for example, “Knights carry large swords, so the squires do too” (factual) and “If knights carry large swords, the squires do too” (possible).

In order to measure the study subjects’ brain activity during these experiments, the researchers deployed magnetoencephalography (MEG), a technique that maps neural activity by recording magnetic fields generated by the electrical currents produced by our brain.

The results showed that factual language led to a rapid increase in neural activity, with the brain responding more powerfully and showing more engagement with fact-based phrases and scenarios compared to those communicating possibility.

“Facts rule when it comes to the brain,” observes Pylkkanen. “Brain regions involved in processing discourse rapidly differentiated facts from possibilities, responding much more robustly to factual statements than to non-factual ones. These findings suggest that the human brain has a powerful, perspective-adjusted neural representation of factual information and, interestingly, much weaker, more elusive cortical signals reflecting the computation of mere possibilities.”

“By investigating language containing clear indicators of possibility compared to factual utterances, we were able to find out which regions of the brain help to rapidly separate non-factual from factual language,” explains Tulling. “Our study thus illustrates how our choice of words has a direct impact on subconscious processing.”

Reference: Tulling et al., “Neural Correlates of Modal Displacement and Discourse-Updating Under (Un)Certainty, eNeuro, DOI: 10.1523/ENEURO.0290-20.2020

Provided by Society for Neuroscience

New Sunspot Cycle Could Be One Of The Strongest On Record (Planetary Science)

Scientists use an extended, 22-year solar cycle to make the forecast.

In direct contradiction to the official forecast, a team of scientists led by the National Center for Atmospheric Research (NCAR) is predicting that the Sunspot Cycle that started this fall could be one of the strongest since record-keeping began.

LEFT: Oppositely charged magnetic bands, represented in red and blue, march toward the equator over a 22-year period. When they meet at the equator, they annihilate one another. RIGHT: The top animation shows the total sunspot number (black) and the contributions from the north (red) and south (blue) hemispheres. The bottom shows the location of the spots. © UCAR

In a new article published inSolar Physics, the research team predicts that Sunspot Cycle 25 will peak with a maximum sunspot number somewhere between approximately 210 and 260, which would put the new cycle in the company of the top few ever observed.

The cycle that just ended, Sunspot Cycle 24, peaked with a sunspot number of 116, and the consensus forecast from a panel of experts convened by the National Aeronautics and Space Administration (NASA) and the National Oceanic and Atmospheric Administration (NOAA) is predicting that Sunspot Cycle 25 will be similarly weak. The panel predicts a peak sunspot number of 115.

If the new NCAR-led forecast is borne out, it would lend support to the research team’s unorthodox theory – detailed in a series of papers published over the last decade – that the Sun has overlapping 22-year magnetic cycles that interact to produce the well-known, approximately 11-year sunspot cycle as a byproduct. The 22-year cycles repeat like clockwork and could be a key to finally making accurate predictions of the timing and nature of sunspot cycles, as well as many of the effects they produce, according to the study’s authors.

“Scientists have struggled to predict both the length and the strength of sunspot cycles because we lack a fundamental understanding of the mechanism that drives the cycle,” said NCAR Deputy Director Scott McIntosh, a solar physicist who led the study. “If our forecast proves correct, we will have evidence that our framework for understanding the Sun’s internal magnetic machine is on the right path.”

The new research was supported by the National Science Foundation, which is NCAR’s sponsor, and NASA’s Living With a Star Program.

SUNSPOT CYCLE 25 STARTS WITH A BANG; WHAT WILL FOLLOW?

In McIntosh’s previous work, he and his colleagues sketched the outline of a 22-year extended solar cycle using observations of coronal bright points, ephemeral flickers of extreme ultraviolet light in the solar atmosphere. These bright points can be seen marching from the Sun’s high latitudes to the equator over about 20 years. As they cross the mid-latitudes, the bright points coincide with the emergence of sunspot activity.

McIntosh believes the bright points mark the travel of magnetic field bands, which wrap around the Sun. When the bands from the northern and southern hemispheres – which have oppositely charged magnetic fields – meet at the equator, they mutually annihilate one another leading to a “terminator” event. These terminators are crucial markers on the Sun’s 22-year clock, McIntosh says, because they flag the end of a magnetic cycle, along with its corresponding sunspot cycle, — and act as a trigger for the following magnetic cycle to begin. 

While one set of oppositely charged bands is about halfway through its migration toward the equatorial meetup, a second set appears at high latitudes and begins its own migration. While these bands appear at high latitudes at a relatively consistent rate — every 11 years — they sometimes slow as they cross the mid-latitudes, which appears to weaken the strength of the upcoming solar cycle.

This happens because the slowdown acts to increase the amount of time that the oppositely charged sets of bands overlap and interfere with one another inside the Sun. The slow-down extends the current solar cycle by pushing the terminator event out in time. Shifting the terminator out in time has the effect of eating away at the spot productivity of thenext cycle.

“When we look back over the 270-year long observational record of terminator events, we see that the longer the time between terminators, the weaker the next cycle,” said study co-author Bob Leamon, a researcher at the University of Maryland Baltimore County. “And, conversely, the shorter the time between terminators, the stronger the next solar cycle is.”

This correlation has been difficult for scientists to see in the past because they have traditionally measured the length of a sunspot cycle from solar minimum to solar minimum, which is defined using an average rather than a precise event. In the new study, the researchers measured from terminator to terminator, which allows for much greater precision. 

While terminator events occur approximately every 11 years and mark the beginning and end of the sunspot cycle, the time between terminators can vary by years. For example, Sunspot Cycle 4 began with a terminator in 1786 and ended with a terminator in 1801, an unprecedented 15 years later. The following cycle, 5, was incredibly weak with a peak amplitude of just 82 sunspots. That cycle would become known as the beginning of the “Dalton” Grand Minimum.

Similarly, Sunspot Cycle 23 began in 1998 and did not end until 2011, 13 years later. Sunspot Cycle 24, which is just ending, was quite weak as well, but it was also quite short — just shy of 10 years long – and that’s the basis for the new study’s bullish prediction that Sunspot Cycle 25 will be strong. 

“Once you identify the terminators in the historical records, the pattern becomes obvious,” said McIntosh. “A weak Sunspot Cycle 25, as the community is predicting, would be a complete departure from everything that the data has shown us up to this point.”

Reference: Title: Overlapping magnetic activity cycles and the sunspot number: Forecasting Sunspot Cycle 25 amplitude
Authors: Scott W. McIntosh, Sandra Chapman, Robert J. Leamon, Ricky Egeland, and Nicholas W. Watkins
Journal: Solar Physics

Provided by UCAR

Brain Clears the Way for Binocular Vision Even Before Eyes are Open (Neuroscience)

To prepare the brain for binocular vision and depth perception, first you have to take out some of the chandeliers.

That’s the takeaway from a group of neurobiologists who studied the development of binocular vision in the mouse brain. They discovered that chandelier cells, so-named because they have many long extensions that control the firing of hundreds of excitatory pyramidal neurons and resemble a chandelier light fixture, are selectively removed from the developing mouse visual cortex even before the animal’s eyes are open by a process of programmed cell death called apoptosis.

A portion of mouse visual cortex shows where the binocular zone is located (green). Chandelier cells are stained red in this image, and the blue is a marker that helped the researchers identify the visual cortex. Chandeliers are clearly less plentiful in the binocular zone. Credit: Bor-Shuen Wang, Cold Spring Harbor Lab

This pruning of about half of the chandelier cells in the second week of development probably clears a path for certain pyramidal neurons to be more active, since chandeliers tend to have a dampening effect on their excitability, explained Josh Huang, a professor of neurobiology in the Duke University School of Medicine. He led this research at his previous position in Cold Spring Harbor Laboratory on Long Island, spearheaded by postdoctoral fellow Bor-Shuen Wang. The findings appear Dec. 7 in the journal Neuron.

“Binocular vision requires fast communication between the two visual hemispheres that receive information in the center visual field,” Huang said. “What we think is that to allow that to happen, the area that mediates this fast communication needs to have reduced inhibition,” accomplished via fewer inhibitory chandelier cells.

The binocular vision enjoyed by mammals like mice and humans is a collaboration of the physical abilities of the eyes and the interpretative abilities of the brain, Huang said. “Many animals (such as a lizard) can see with both eyes, but their processing of visual information from each eye is largely separate. Only in most mammals is there a central part of the visual world that is seen by both eyes and it is the brain that has to combine the left and right visual images into a coherent single perception.”

Some of the binocular system is laid down by genetic instructions that build the structures of the visual pathways, but the finer visual circuits are shaped by visual experience.

“The whole process of brain development is a continuous process in which genetic information plays a major role in constructing larger scaffold of the brain network,” Huang said. “But later, there are learning- and experience-dependent processes that begin to customize many of the details of the brain circuits for each individual. The phenomenon we’re talking about is right at the juncture between the genetic-instructed and use-dependent mechanisms,” Huang said.

Adding to the complexity, the brain processes binocular vision in two different and coordinated ways, Huang said. As signals travel from the left and right retina to the thalamus, some signals cross to the other side of the brain, and others don’t, but they converge in the visual cortex, thereby contributing to binocular vision. The second path is that the left and right visual cortexes, receiving information from the retina, communicate through callosal neurons via the corpus callosum, a connection between brain hemispheres. That further sharpens binocular vision.

In that second week after birth and before their eyes open, the retinas of the developing mouse generate waves of activity that help organize the visual cortex by reducing the density of the inhibitory chandelier cells. This is achieved by instructing the callosal neurons to literally kill half of the chandelier cells. The researchers showed that blocking those retinal inputs prevented chandelier cell pruning in the visual cortex.

When they experimentally prevented the chandelier pruning in some mice, those mice flunked a 3-D visual perception test, but otherwise seemed to see and behave normally. To confirm that the chandelier pruning is driven by retinal activity without any visual input, pups were raised in complete darkness. And the chandelier pruning still happened.

“Most likely, that killing of chandelier cells by callosal neurons is not random but is a step of proper binocular circuit assembly,” Huang said. As young chandelier cells begin to form connections, those that form the “wrong connections” that may slow down the callosal pathway are likely to be selectively killed, while others that contribute to other aspects of visual processing are preserved. When pruning was blocked, a significant portion of the remaining chandelier cells appeared stunted. Those, he thinks, are the ones that would have been pruned.

Reference: “Retinal and Callosal Activity-Dependent Chandelier Cell Elimination Shapes Binocularity in Primary Visual Cortex,” Bor-Shuen Wang, Maria Sol Bernardez Sarria, An Xu, Miao He, Nazia M. Alam, Glen T. Prusky, Michael C. Crair, Z. Josh Huang. Neuron (2020). DOI: 10.1016/j.neuron.2020.11.004

Provided by Duke University School of Nursing

Gut Research Identifies Key Cellular changes Associated with Childhood-onset Crohn’s Disease (Medicine)

Scientists have tracked the very early stages of human foetal gut development in incredible detail, and found specific cell functions that appear to be reactivated in the gut of children with Crohn’s Disease. The results are an important step towards better management and treatment of this devastating condition.

Emerging intestinal villi with green stem cells supporting their growth Credit: Kenny Roberts & Sophie Pritchard, Wellcome Sanger Institute

The research from the University of Cambridge and the Wellcome Sanger Institute is part of the global Human Cell Atlas initiative to map every cell type in the human body. The findings reveal intricate cellular mechanisms of how the gut develops.

Crohn’s Disease is a type of Inflammatory Bowel Disease affecting around one in every 650 people in the UK. Incidence has increased dramatically in recent decades, especially in children – who can suffer very aggressive symptoms including abdominal pain, diarrhoea and fatigue. This lifelong condition can have major life implications; the cause is not understood, treatments often don’t work, and there is no cure.

“Crohn’s Disease can be particularly aggressive and more treatment-resistant in children, so there’s a real need to understand the condition when it affects them and perhaps come up with childhood-specific treatments,” said Dr Matthias Zilbauer in the Department of Paediatrics at the University of Cambridge and honorary consultant in paediatric gastroenterology at Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, who led the study.

The researchers used a cutting-edge technology called single-cell RNA sequencing to look at gene expression in individual cells of the developing human gut, six to ten weeks after conception. They focused on the inner lining of the gut, called the intestinal epithelium, and found that the cells there divide constantly at this early stage, guided by messages from other cell types. This allows the gut to grow and form the structures needed for good gut function later in life.

Tissues from the guts of children with Crohn’s Disease, aged between four and twelve, were also analysed. The study revealed that some of the cellular pathways active in the epithelium of the foetal gut appear to be reactivated in Crohn’s Disease. These pathways were not active in healthy children of a similar age. The results are published today in the journal Developmental Cell.

“Our results indicate there might be a reprogramming of specific gut cell functions in Crohn’s Disease. We don’t know whether this is the cause of the disease or a consequence of it, but either way it is an exciting step in helping us to better understand the condition,” said Zilbauer.

The findings shed light on fundamental molecular mechanisms of human gut development. The team also found that lab-grown ‘mini-guts’ undergo similar individual cellular changes to those inside a developing foetus. This implies that lab-grown models are a powerful and accurate tool for future research into very early gut development and associated diseases.

“This study is part of the international Human Cell Atlas effort to create a ‘Google map’ of the entire human body. With single-cell RNA sequencing we can look at any tissue and identify the individual cell types it’s made up of, the function of those cells, and even identify new cell types,” said Dr Sarah Teichmann at the Wellcome Sanger Institute, and co-chair of the Human Cell Atlas Organising Committee, whose expertise enabled analysis of the huge amount of data generated by this technique.

She added: “A complex tissue like the gut contains different cell types, and these ‘talk’ to each other – the function of one cell affects the function of another. That’s particularly important in the early stages of gut development, and something we can interrogate using computational analyses of single cell RNA sequencing data.”

While the study focused specifically on the dynamics of intestinal epithelial cells, it generated information on around 90,000 primary human intestinal cells of all types. The researchers have made this data openly available at http://www.gutcellatlas.org, creating a valuable resource for further research and drug discovery targeted at childhood Crohn’s Disease.

“From my own experience we’re diagnosing Crohn’s Disease in younger and younger children, some even under the age of five – it’s very much an emerging disease. It’s a really nasty, lifelong condition, and when children are diagnosed, the whole family is affected,” said Zilbauer.

He added: “We are determined to advance our knowledge in this area, and hopefully improve the lives of these children in the future.”

Provided by University of Cambridge

Researchers Study the Manipulation of Bone Marrow Stem Cells into Innate Lymphoid and Natural Killer Cells (Medicine)

Children’s Hospital Colorado (Children’s Colorado) Center for Cancer and Blood Disorders (CCBD) announced today that a study about the manipulation of bone marrow stem cells into innate lymphoid and natural killer cells will be published in Science Immunology, a well-respected, high-impact medical journal.

Hematopoietic precursor cells: promyelocyte in the center, two metamyelocytes next to it and band cells from a bone marrow aspirate. Credit: Bobjgalindo/Wikipedia

It is well established that bone marrow stem cells give rise to all types of blood cells. However, the conditions that drive this process are not understood. The Children’s Colorado research conducted on the Anschutz Medical Campus characterizes how the cancer fighting Natural Killer (NK) cells develop. The work also shows how another blood cell type, called “innate lymphoid cells” develop. This latter cell type is involved in many aspects of human health and disease.

By understanding these factors, researchers will be able to manipulate the stem cells and tailor therapies for children and adults who are receiving cancer treatments in the years to come. Based on the results of the Children’s Colorado CCBD study, the team applied for intellectual property protection around the methods used in the research, and the paper was accepted by Science Immunology.

“We are very encouraged by the results of this study and believe the results will help us better treat children and adults in the future,” said Mike Verneris, MD, professor, Pediatrics-Hematology/Oncology and Bone Marrow Transplantation. “This significant research and subsequent publication in Science Immunology distinguishes Children’s Colorado as a leader in the medical community and sets us up for meaningful advances in cancer treatment and therapies in the future.”

As the holder of the Barton Family Endowed Chair in Bone Marrow Transplant, Dr. Verneris has relied on philanthropic support to advance his groundbreaking research. In addition to federal research funding, the investment of generous donors played a critical role in this breakthrough.

Reference: Dejene M. Tufa et al, Human innate lymphoid cell precursors express CD48 that modulates ILC differentiation through 2B4 signaling, Science Immunology (2020). DOI: 10.1126/sciimmunol.aay4218

Provided by Children’s Hospital Colorado

Researchers Find Seventeen Genetic Abnormalities that Cause Brain Aneurysms (Psychiatry)

Nearly three percent of the world’s population is at risk of developing an intracranial aneurysm, a localized dilation of a blood vessel forming a fragile pocket. Rupture of this aneurysm results in extremely severe, and, in one-third of cases, fatal hemorrhage. In the framework of the International Stroke Genetics Consortium, a team led by the University of Geneva (UNIGE), the University Hospitals of Geneva (HUG) and the University of Utrecht is studying the genetic determinants of aneurysms in order to better understand the different forms of the disease and to assess individual risk. Through the examination of the genome of more than 10,000 people suffering from aneurysms compared to that of 300,000 healthy volunteers, 17 genetic abnormalities have been identified that are notably involved in the functioning of the vascular endothelium, the inner lining of blood vessels. In addition, the scientists discovered a potential link between these genetic markers and anti-epileptic drugs, making it possible to consider the use of certain drugs in the management of the disease. These results, to be read in the journal Nature Genetics, also highlight how the wise use of large databases containing genomic and phenotypic information can advance research.

An aneurysm is a natural dome (in blue) that usually grows at an intracerebral arterial bifurcation aimed at decreasing the friction forces (in red) and thus allowing the vessel to heal. Multiple factors participate in the healing of the vessel wall; danger comes however from the risk of rupture. Credit: UNIGE-HUG

Every year, five out of every 100,000 people experience a rupture of an intracranial aneurysm—as many as those injured in road accidents. And only very rapid and highly specialized surgical management can hope to save their lives. “It is therefore essential to better understand the genetic basis—inherited or otherwise—governing the risk of developing the disease, but also to distinguish between the different forms of the disease and its severity. This will allow us to detect people at risk and offer them the most appropriate treatment,” explains Philippe Bijlenga, Assistant Professor in the Department of Clinical Neurosciences at UNIGE Faculty of Medicine and Senior Consultant at HUG Division of Neurosurgery, who led the Swiss part of this study. This multipronged disease, whose evolution depends on genetic, congenital and environmental factors, is indeed complex to apprehend. “The tiny variations that make it up must therefore be deciphered,” he adds.

A study of unprecedented scope

The work carried out in Geneva and Utrecht is the largest genetic study in the world in the field of intracranial aneurysms. The DNA of more than 10,000 patients was examined and compared with that of 300,000 volunteers: eleven new regions of the genome—compared with six previously—were found to be associated with the disease. “Each of these DNA variations causes a slight increase in the risk of an intracranial aneurysm,” says Ynte Ruigrok, neurologist and associate professor at the University Medical Center of Utrecht University, who co-led the study. “Thus, their accumulation can, together, constitute a significant risk.”

Most of these genetic abnormalities appear to be related to the functioning of the endothelial cells that line the inside of blood vessels and usually make them robust. “These cells have long been suspected of being responsible for aneurysms,” says Philippe Bijlenga. “We now have evidence that leads us to work on possible markers of instability that could indicate whether the aneurysm is stable, healed, or at high risk of adverse outcomes.”

In addition, this research shows that a genetic predisposition to high blood pressure and smoking play an important role in the development of an intracranial aneurysm. If these risk factors were already known from a clinical and epidemiological point of view, we now have the genetic evidence.

The scientists also made a surprising discovery: “It appears that the protein structures of some of the genes we identified are linked to antiepileptic drugs. We do not yet know whether this effect is positive or negative, but it opens up the possibility for pharmacological treatments, potentially less invasive than the surgical approaches we are currently using,” says Philippe Bijlenga. The scientists will now work on modeling the disease, both biologically and therapeutically, to offer physicians a medical decision support system that will help determine potential management protocols based on each person’s genetic data.

Scientific advances and data protection

To carry out these studies, the research teams must have access to a very large number of patients, and therefore work in international consortia. “To achieve this, we have set up tools to standardize complex data. We had to find a common language, unify clinical evaluation criteria, imaging methods and their computer processing, and establish exchange structures while guaranteeing the protection of personal data,” reports Philippe Bijlenga, who supervised this work on data.

The consortium has set up a structure capable of collecting, harmonizing and securing huge amounts of data. The Swiss Institute of Bioinformatics (SIB) manages the phenotypic data, while the University of Utrecht stores the genomic data. Both datasets are accessible through an approval process to research teams around the world. “However, proper use must be demonstrated. Our system allows scientific advances, but with protection of personal data,” the authors conclude.

Reference: Bakker, M.K., van der Spek, R.A.A., van Rheenen, W. et al. Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors. Nat Genet 52, 1303–1313 (2020). https://doi.org/10.1038/s41588-020-00725-7 https://www.nature.com/articles/s41588-020-00725-7

Provided by University of Geneva

Weekly Folic Acid Boost Shows Potential to Halve Birth Defects (Medicine)

SAHMRI researchers have found the risk of birth defects can be greatly reduced if women significantly increase their folic acid intake.

Neural tube defects (NTDs) are birth defects like spina bifida that effect 300,000 babies born annually worldwide. Some of these babies die at birth while others have life-long disabilities.

The study sponsored by Nutrition International with support from the Government of Canada and published in BMJ Global Health, has shown taking weekly iron folic acid supplements (IFA) containing 2.8 mg folic acid can lower the risk of NTDs by up to four times more than the current global standard of just 0.4 mg.

Project leader, Professor Tim Green said during the trial, 70% of women consuming 2.8 mg folic acid per week achieved a red blood cell folate concentration associated with a low NTD risk, compared with just 10% of those taking 0.4 mg.

“A folic acid supplement should be taken not only by those who are planning a pregnancy, but by all women who are sexually active,” Prof Green said.

“We know around half of pregnancies are unplanned globally and in low and middle income countries 10 million of these pregnancies occur each year in adolescents alone. By the time these women realize they’re pregnant it’s too late to get the benefits of IFA.”

Researchers predict the number of NTDs worldwide could be halved if the World Health Organization (WHO) acts on the latest findings.

The WHO currently recommends a weekly supplement for all women aged 15-49 living in countries where the rate of anemia is above 20%. This supplement currently contains the appropriate 60mg of iron but just 0.4mg of folic acid; not enough to provide a benefit.

“It’s our recommendation that the optimal 2.8mg of folic acid formulation be made widely available to women in low and middle income countries as soon as possible,” Prof Green said.

Reference: Kaitlyn L I Samson et al. Weekly iron–folic acid supplements containing 2.8 mg folic acid are associated with a lower risk of neural tube defects than the current practice of 0.4 mg: a randomized controlled trial in Malaysia, BMJ Global Health (2020). DOI: 10.1136/bmjgh-2020-003897 https://gh.bmj.com/content/5/12/e003897

Provided by BMJ Global Health